ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.4347A>G (p.Ser1449=)

gnomAD frequency: 0.01042  dbSNP: rs719202
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040320 SCV000064011 benign not specified 2012-07-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000040320 SCV000153290 benign not specified 2015-02-10 criteria provided, single submitter clinical testing
GeneDx RCV000040320 SCV000169504 benign not specified 2014-04-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000231821 SCV000286660 benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-02-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000329402 SCV000425042 benign Tibial muscular dystrophy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000386361 SCV000425043 likely benign Autosomal recessive limb-girdle muscular dystrophy type 2J 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000294226 SCV000425044 benign Early-onset myopathy with fatal cardiomyopathy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000332797 SCV000425045 benign Myopathy, myofibrillar, 9, with early respiratory failure 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000279046 SCV000425047 likely benign Dilated cardiomyopathy 1G 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics RCV000618691 SCV000735744 benign Cardiovascular phenotype 2015-05-27 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769130 SCV000900504 benign Cardiomyopathy 2016-03-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040320 SCV001360630 benign not specified 2019-11-06 criteria provided, single submitter clinical testing Variant summary: TTN c.4347A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0028 in 250952 control chromosomes, predominantly at a frequency of 0.039 within the African or African-American subpopulation in the gnomAD database, including 21 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 62-folds over the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. A co-occurrence with another pathogenic variant has been reported (TTR c.424G>A, p.V142I). Five ClinVar submissions (evaluation after 2014) cite the variant as four times as benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab RCV000386361 SCV002101509 benign Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000332797 SCV002101510 benign Myopathy, myofibrillar, 9, with early respiratory failure 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000294226 SCV002101511 benign Early-onset myopathy with fatal cardiomyopathy 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000329402 SCV002101513 benign Tibial muscular dystrophy 2021-09-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001795028 SCV004562778 benign not provided 2022-12-21 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV001795028 SCV005262327 likely benign not provided criteria provided, single submitter not provided
Clinical Genetics, Academic Medical Center RCV000040320 SCV001918362 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000040320 SCV001967131 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001795028 SCV002036972 likely benign not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.